Developing an enzyme-assembled phytoglycogen-based carrier for intestinal-targeted delivery of metformin

Enzymatic assembly forms pH-responsive CMPG-Gel ensuring high load efficiency. • pH-triggered volume/zeta potential shifts enable targeted intestinal drug release. • High metformin loading (97.5%) via H-bonding and pH-dependent release • Structural analysis confirms Met entrapment and rheology shows elastic dominance. • Enzymatic assembly with PG creates sustainable oral delivery platform. Oral metformin (Met) delivery is limited by gastric degradation and low bioavailability, necessitating intestinal-targeted systems. A pH-responsive carboxymethylated phytoglycogen (PG) hydrogel (CMPG-Gel) was fabricated via enzyme-catalyzed assembly to address this issue. Optimal preparation conditions of gel were: 8% PG or CMPG substrate concentration, 1:6 substrate/glucose -1- phosphate (Glc-1-P) monomer ratio, 0.6 mL enzyme dosage, and 0.25 degree of substitution (DS). The xerogel exhibited excellent water-swelling capacity and efficient Met loading. Enzyme-assisted assembly achieved a 39.00 ± 1.49 mg/g loading capacity and 97.50% ± 0.90% efficiency, superior to physical adsorption. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and independent gradient model (IGM) analyses confirmed Met stabilization in the hydrogel network via hydrogen bonding. Rheological data (G' > G”) indicated solid-like viscoelastic behavior. The pH-responsive mechanism of CMPG-Gel relied on carboxyl group ionization: low-pH protonation of carboxyl group caused gel contraction, whereas high-pH deprotonation enhanced gel swelling via electrostatic repulsion. In vitro studies demonstrated pH-dependent Met release, 52.28% in simulated gastric fluid (SGF) and 98.05% in simulated intestinal fluid (SIF), achieving effective intestinal-targeted delivery.